Clinical Implication of Non-Complement-Binding Donor-Specific Anti-HLA Antibodies in Heart Transplant Recipients -Risk Stratification by C1q-Binding Capacity

Takuma Sato, Osamu Seguchi, Yoshiaki Kanaumi, Yuto Kumai, Sachi Matsuda, Haruki Sunami, Kensuke Kuroda, Yorihiko Matsumoto, Seiko Nakajima, Koji Arai, Kyoichi Wada, Hiroki Hata, Satsuki Fukushima, Masanobu Yanase, Hatsue Ishibashi-Ueda, Tomoyuki Fujita, Junjiro Kobayashi and Norihide Fukushima

Department of Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan
Department of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Department of Pharmacy, National Cerebral and Cardiovascular Center, Osaka, Japan
Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan
Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, Japan

^*Correspondance to: Norihide Fukushima 

 PDF  Full Text DOI: 10.25107/2474-1647.1703

Abstract

Background: The development of de novo human leukocyte antigen (HLA) donor specific antibodies (DSA), detected by either cytotoxic or solid phase assays, was considered the major risk factor for cardiac graft failure in heart transplantation. However, it was shown that not all patients with persistent production of DSA suffered loss of their allografts. The ability to activate complement may be an important factor differentiating clinically relevant DSA from non- relevant DSA. Recently, a C1q-binding assay (C1qScreen; One Lambda, Inc. Canoga Park, CA) has been developed to identify complement-fixing HLA antibodies with high sensitivity and specificity. The aim of this study was to investigate the association between C1q-binding ability of HLA-DSA and the clinical outcomes post-transplant to identify clinically significant DSA after heart transplantation.Methods: We enrolled 64 consecutive patients who received heart transplant between May 1999 and January 2015 in our institute. Sixty of 64 patients (93.7%) were screened for the presence of circulating DSA using Luminex Single Antigen Flow Bead assays between June 2014 and August 2015, and patients with post-transplant DSA with mean fluorescence intensity (MFI) >500 were selected to assess C1q fixation by C1q-binding assays. The clinical outcomes were compared with the results.Results: Of 60 patients, twelve patients were considered as DSA positive (MFI >500, range 698-5952, class 1: 75% class 2: 17%, class1+2: 8%). All of these patients were identified as C1q negative. As the results, we divided into two groups; group C1q negative DSA (n=12) and group non-DSA (n=48). The rejection episodes, cardiac events, mortality, the development of cardiac graft vasculopathy and cardiac function were not statistically different between the two groups.Conclusion: Patients producing C1q-negative DSA had good graft survival, which was comparable to that of DSA negative patients. Adding the assessment of the complement-binding capacity of DSA might redefine the traditional risk stratification of DSA positive patients after heart transplantation.

Keywords

Heart transplantation; Donor specific antibodies; Antibody mediated rejection; C1q; Complement-binding ability

Cite the article

Sato T, Seguchi O, Kanaumi Y, Kumai Y, Matsuda S, Sunami H, et al. Clinical Implication of Non-Complement-Binding Donor-Specific Anti-HLA Antibodies in Heart Transplant Recipients -Risk Stratification by C1q-Binding Capacity. Clin Surg. 2017; 2: 1703.